The overall project objective is to carry forward a collaborative program of tropical parasitic disease research on several basic problems which underlie the major health priorities of the Republic of Sudan. The solutions we seek should permit inferences to be drawn which are of value to those involved in the characterization, prevention, treatment and control of parasitic diseases elsewhere in the tropics. Four widespread and important human parasitoses will be addressed: malaria, schistosomiasis, onchocerciasis and leishmaniasis. Malaria is by far the most important disease in Sudan; in the absence of chemotherapeutic or vector control interventions the outcome of infection is largely the result of host-immune response - parasite interactions. The nature of these, specifically with regard to T cell responsiveness to defined antigens and the pattern of cell-mediated effector mechanisms in well characterized subsets of endemic area populations form the focus for proposal #1. Contemporary approaches to schistosomiasis in the field depend on widespread use of anthelmintic drugs. The accurate assessment of their impact in terms of pathology and its resolution has only recently become possible using non-invasive ultrasound technology. In proposal #2 we extend our findings on cross-sectional analysis of Symmer;s fibrosis in affected communities to include biochemical and immunological correlates of the onset and disposition of pathologic changes in this most important component of schistosomal disease. The potential impact of ivermectin, a newly developed microfilaricidal agent, on onchocerciasis in Sudan is enormous. However, major questions remain about its pharmacology and mode of action and the role of host-immune responses in its efficacy in vivo and the adverse consequences of treatment. These will be explored in proposal #3 on onchocerciasis. Leishmaniasis, common in rural areas of eastern Sudan, involves immune mechanisms in its pathogenesis which are not well characterized. Longitudinal monitoring of cell-mediated and immunoglobulin types of responses in persons at different disease stages and during and after treatment will be used to establish mechanisms in its pathogenesis which are not well characterized. Longitudinal monitoring of cell-mediated and immunoglobulin types of responses in persons at different disease stages and during and after treatment will be used to establish mechanisms that operate in pathogenesis and after treatment will be used to establish mechanisms that operate in pathogenesis and in the onset of cure and perhaps protection (Project #4. Sustained involvement of Sudanese administrators, professionals, and technicians throughout this program will ensure enhancement of national research capacity for the future, and the research results should contribute to improvements in health care for the affected human populations throughout the country.